α-Synuclein is a protein consisting of 140 residues of amino acids encoded by the SNCA gene, and it is expressed richly in the presynaptic terminal in the brain. Synucleinopathies are a group of neurodegenerative diseases characterized by the abnormal accumulation of α-synuclein, and known examples include an accumulation in the Lewy bodies/neurites in the Lewy bodies dementia, and an accumulation of glial cytoplasmic inclusion of multiple system atrophy. It has been reported that a polyunsaturated fatty acid is involved in the oligomerization of α-synuclein (Non-patent documents 1 and 2). These days, in this country where the society is aging rapidly, the number of patients suffering a disease that can be categorized as synucleinopathy is considerably increasing.
Fatty Acid Binding Protein (FABP) is a cytoplasm-type protein having a low molecular weight (14 to 15 kDa), and it shows tissue specific expression. FABP holds as its ligand, a middle chain to long chain fatty acid, and is believed to be involved in the retention of homeostasis or transduction of signals in a lipid metabolism. FABP is known to have multiple subtypes with mutually analogous molecule structures. FABP3 is expressed in the heart, and although its function is not fully elucidated, it is believed to be involved in the lipid homeostasis such as the incorporation of lipid, and the transportation to β-oxidation in mitochondria. There has been a report of a compound having an inhibitory activity against FABP3 (Non-patent Document 2). There has also been a report that FABP3 accelerates the α-synuclein aggregation (Non-patent Document 1).
In the Parkinson's disease, the α-synuclein aggregate (inclusion) appears in the substantia nigra dopamine neurons, and in the dementia with Lewy bodies, it appears in a diffuse state in the cerebral cortex. When the filamentous synuclein is injected into a rat corpus striatum, the aggregate is propagated to the cerebral cortex as well as the substantia nigra, and forms a synuclein inclusion in the nerve cell (Non-patent Document 3).